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Combination Chemotherapy Followed by Donor Stem Cell Transplant in Treating Patients With Relapsed or High-Risk Primary Refractory Hodgkin Lymphoma

Primary Purpose

Lymphoma

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
cyclophosphamide
cyclosporine
fludarabine phosphate
gemcitabine hydrochloride
ifosfamide
mechlorethamine hydrochloride
melphalan
methotrexate
mycophenolate mofetil
prednisone
procarbazine hydrochloride
vincristine sulfate
vinorelbine tartrate
allogeneic bone marrow transplantation
allogeneic hematopoietic stem cell transplantation
nonmyeloablative allogeneic hematopoietic stem cell transplantation
peripheral blood stem cell transplantation
umbilical cord blood transplantation
total-body irradiation
Sponsored by
Memorial Sloan Kettering Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Lymphoma focused on measuring recurrent adult Hodgkin lymphoma, recurrent/refractory childhood Hodgkin lymphoma, adult lymphocyte depletion Hodgkin lymphoma, adult nodular sclerosis Hodgkin lymphoma, adult mixed cellularity Hodgkin lymphoma, childhood lymphocyte depletion Hodgkin lymphoma, childhood mixed cellularity Hodgkin lymphoma, childhood nodular sclerosis Hodgkin lymphoma, stage III adult Hodgkin lymphoma, stage IV adult Hodgkin lymphoma, stage III childhood Hodgkin lymphoma, stage IV childhood Hodgkin lymphoma

Eligibility Criteria

13 Years - 65 Years (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

DISEASE CHARACTERISTICS:

  • Histologically confirmed classical Hodgkin lymphoma, including CD20+ disease

    • No lymphocyte predominant histology

  • Primary refractory or relapsed disease with all 3 risk factors, failed platinum-based chemotherapy, or disease relapsed more than 100 days after autologous stem cell transplantation, proven by biopsy or fine-needle aspiration (cytology) of an involved site

    • Risk factors are defined as B-symptoms, extranodal sites of disease, and disease remission lasting < 1 year after first-line therapy
  • Failed doxorubicin hydrochloride or mechlorethamine hydrochloride-containing front-line therapy
  • Fludeoxyglucose F 18-PET scan demonstrating PET-avid disease
  • No more than 2 prior salvage chemotherapy regimens (for patients proceed to allogeneic hematopoietic stem cell transplantation [AHSCT])

  • Donor available meeting 1 of the following criteria (for patients proceed to AHSCT):

    • HLA-matched or one allele mismatched related donor

      • Genotypically or phenotypically matched at ≥ 9/10 of the A, B, C, DRB1, and DQB1 loci, as tested by high resolution
      • Peripheral blood stem cells (PBSC) collected

    • HLA-matched unrelated donor

      • Matched at ≥ 9/10 (allele mismatch only) of the A, B, C, DRB1, and DQB1 loci, as tested by high resolution
      • PBSC or bone marrow collected

    • Umbilical cord blood (2 units)

      • must be ≥ 4/6 HLA-A, B antigen, and DRB1 allele matched with recipient

PATIENT CHARACTERISTICS:

  • Platelet count > 50,000/mm^3
  • ANC > 1,000/mm^3
  • Cardiac ejection fraction > 50% (for patients ≥ 18 years of age)
  • Fractional shortening > 50% by echocardiogram* (for patients < 18 years of age)
  • Adjusted diffusing capacity > 50% on pulmonary function testing*
  • Serum creatinine < 1.5 mg/dL
  • Creatinine clearance ≥ 50 mL/min
  • Total bilirubin < 2.0 mg/dL in the absence of a history of Gilbert disease
  • HIV I and II negative
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • Karnofsky performance status (PS) ≥ 70% or Lansky PS ≥ 70% (for patients proceed to AHSCT)
  • No active and uncontrolled infection at time of transplantation including active infection with Aspergillus or other mold (for patients proceed to AHSCT) NOTE: *measured since last chemotherapy

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • No prior allogeneic transplantation
  • No more than 1 prior autologous transplantation
  • No inability to complete planned cytoreduction due to therapy complications

Sites / Locations

  • Memorial Sloan-Kettering Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

High-Risk or Relapsed Hodgkin Lymphoma

Arm Description

This is a phase 2 intention-to-treat study of salvage chemotherapy followed by allogeneic HSC transplant for the treatment of primary refractory or relapsed HL. Patients who 1) do not progress on salvage chemotherapy, and 2) have both suitable HSC donors and 3) a satisfactory pre-allograft work-up will proceed to allograft. Patients who fail any of these 3 criteria will be off-study and considered treatment failures for the purposes of the intention-to-treat study.

Outcomes

Primary Outcome Measures

Progression-free Survival at 1 Year
Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions

Secondary Outcome Measures

Overall Survival
Disease Relapse or Progression as Measured by CT Scan or PET

Full Information

First Posted
December 14, 2007
Last Updated
September 7, 2023
Sponsor
Memorial Sloan Kettering Cancer Center
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00574496
Brief Title
Combination Chemotherapy Followed by Donor Stem Cell Transplant in Treating Patients With Relapsed or High-Risk Primary Refractory Hodgkin Lymphoma
Official Title
An Intention-to-Treat Study of Salvage Chemotherapy Followed by Allogeneic Hematopoietic Stem Cell Transplant for the Treatment of High-Risk or Relapsed Hodgkin Lymphoma
Study Type
Interventional

2. Study Status

Record Verification Date
October 2022
Overall Recruitment Status
Completed
Study Start Date
November 13, 2007 (Actual)
Primary Completion Date
August 2, 2022 (Actual)
Study Completion Date
August 2, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Memorial Sloan Kettering Cancer Center
Collaborators
National Cancer Institute (NCI)

4. Oversight

5. Study Description

Brief Summary
RATIONALE: Giving chemotherapy before a donor stem cell transplant helps stop the growth of cancer cells. It also helps stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving cyclosporine, mycophenolate mofetil, and methotrexate before and after transplant may stop this from happening. PURPOSE: This phase II trial is studying how well combination chemotherapy followed by donor stem cell transplant works in treating patients with relapsed or high-risk primary refractory Hodgkin lymphoma.
Detailed Description
OUTLINE: Patients are stratified according to response to prior therapy and risk factors (those with presence of all 3 risk factors and failed primary therapy or primary progressive disease vs. patients who relapse more than 100 days after an autologous stem cell transplant). Salvage chemotherapy (IGV or MOPP): Patients who have previously received mechlorethamine hydrochloride receive IGV; patients who have previously received a gemcitabine-based regimen receive MOPP. IGV (ifosfamide, gemcitabine hydrochloride, and vinorelbine ditartrate): Patients receive IGV combination chemotherapy comprising ifosfamide IV on days 1-4, gemcitabine hydrochloride IV on days 1 and 4, and vinorelbine ditartrate IV on day 1. Treatment repeats every 2-3 weeks for 2-3 courses in the absence of disease progression or unacceptable toxicity. MOPP (mechlorethamine hydrochloride, vincristine, procarbazine hydrochloride, and prednisone): Patients receive MOPP combination chemotherapy comprising mechlorethamine hydrochloride IV on days 1 and 8, vincristine IV on days 1 and 8, oral procarbazine hydrochloride on days 1-14, and oral prednisone on days 1-14. Treatment repeats every 4 weeks for at least 2 courses in the absence of disease progression or unacceptable toxicity. Patients with no progression of disease after salvage chemotherapy (at allograft work-up) proceed to allogeneic hematopoietic stem cell transplantation [AHSCT]* within 60 days after completion of salvage chemotherapy. NOTE: *Patients with a nodal mass > 5 cm that has not ben previously irradiated and in the absence of extranodal disease may undergo involved-field radiotherapy twice daily for 2 weeks, prior to AHSCT. AHSCT with reduced-intensity or non-myeloablative conditioning: Patients achieving partial response or stable disease after salvage therapy receive fludarabine phosphate IV over 30 minutes on days -6 to -2; melphalan IV over 15 minutes on days -6 and -5; and undergo AHSCT on day 0 (reduced-intensity conditioning). Patients achieving complete response after salvage therapy receive fludarabine phosphate IV over 30 minutes on days -6 to -2; cyclophosphamide IV over 15 minutes on day -6; total-body irradiation over 20-30 minutes on day -1; and undergo AHSCT on day 0 (non-myeloablative conditioning). Graft-vs-host disease prophylaxis: Patients with related or unrelated donors receive cyclosporine IV over 2-4 hours or orally on days -3 to 100 followed by a taper, mycophenolate mofetil IV or orally on days -3 to 46 followed by a taper, and methotrexate IV on days 1, 3, 6, and 11. Patients who received umbilical cord blood receive cyclosporine and mycophenolate mofetil as above (no methotrexate). Follow-up period of 2 years post-transplant.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lymphoma
Keywords
recurrent adult Hodgkin lymphoma, recurrent/refractory childhood Hodgkin lymphoma, adult lymphocyte depletion Hodgkin lymphoma, adult nodular sclerosis Hodgkin lymphoma, adult mixed cellularity Hodgkin lymphoma, childhood lymphocyte depletion Hodgkin lymphoma, childhood mixed cellularity Hodgkin lymphoma, childhood nodular sclerosis Hodgkin lymphoma, stage III adult Hodgkin lymphoma, stage IV adult Hodgkin lymphoma, stage III childhood Hodgkin lymphoma, stage IV childhood Hodgkin lymphoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
25 (Actual)

8. Arms, Groups, and Interventions

Arm Title
High-Risk or Relapsed Hodgkin Lymphoma
Arm Type
Experimental
Arm Description
This is a phase 2 intention-to-treat study of salvage chemotherapy followed by allogeneic HSC transplant for the treatment of primary refractory or relapsed HL. Patients who 1) do not progress on salvage chemotherapy, and 2) have both suitable HSC donors and 3) a satisfactory pre-allograft work-up will proceed to allograft. Patients who fail any of these 3 criteria will be off-study and considered treatment failures for the purposes of the intention-to-treat study.
Intervention Type
Drug
Intervention Name(s)
cyclophosphamide
Intervention Type
Drug
Intervention Name(s)
cyclosporine
Intervention Type
Drug
Intervention Name(s)
fludarabine phosphate
Intervention Type
Drug
Intervention Name(s)
gemcitabine hydrochloride
Intervention Type
Drug
Intervention Name(s)
ifosfamide
Intervention Type
Drug
Intervention Name(s)
mechlorethamine hydrochloride
Intervention Type
Drug
Intervention Name(s)
melphalan
Intervention Type
Drug
Intervention Name(s)
methotrexate
Intervention Type
Drug
Intervention Name(s)
mycophenolate mofetil
Intervention Type
Drug
Intervention Name(s)
prednisone
Intervention Type
Drug
Intervention Name(s)
procarbazine hydrochloride
Intervention Type
Drug
Intervention Name(s)
vincristine sulfate
Intervention Type
Drug
Intervention Name(s)
vinorelbine tartrate
Intervention Type
Procedure
Intervention Name(s)
allogeneic bone marrow transplantation
Intervention Type
Procedure
Intervention Name(s)
allogeneic hematopoietic stem cell transplantation
Intervention Type
Procedure
Intervention Name(s)
nonmyeloablative allogeneic hematopoietic stem cell transplantation
Intervention Type
Procedure
Intervention Name(s)
peripheral blood stem cell transplantation
Intervention Type
Procedure
Intervention Name(s)
umbilical cord blood transplantation
Intervention Type
Radiation
Intervention Name(s)
total-body irradiation
Primary Outcome Measure Information:
Title
Progression-free Survival at 1 Year
Description
Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions
Time Frame
1 year
Secondary Outcome Measure Information:
Title
Overall Survival
Time Frame
up to 8 years
Title
Disease Relapse or Progression as Measured by CT Scan or PET
Time Frame
3 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
13 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
DISEASE CHARACTERISTICS: Histologically confirmed classical Hodgkin lymphoma, including CD20+ disease No lymphocyte predominant histology Primary refractory or relapsed disease with all 3 risk factors, failed platinum-based chemotherapy, or disease relapsed more than 100 days after autologous stem cell transplantation, proven by biopsy or fine-needle aspiration (cytology) of an involved site Risk factors are defined as B-symptoms, extranodal sites of disease, and disease remission lasting < 1 year after first-line therapy Failed doxorubicin hydrochloride or mechlorethamine hydrochloride-containing front-line therapy Fludeoxyglucose F 18-PET scan demonstrating PET-avid disease No more than 2 prior salvage chemotherapy regimens (for patients proceed to allogeneic hematopoietic stem cell transplantation [AHSCT]) Donor available meeting 1 of the following criteria (for patients proceed to AHSCT): HLA-matched or one allele mismatched related donor Genotypically or phenotypically matched at ≥ 9/10 of the A, B, C, DRB1, and DQB1 loci, as tested by high resolution Peripheral blood stem cells (PBSC) collected HLA-matched unrelated donor Matched at ≥ 9/10 (allele mismatch only) of the A, B, C, DRB1, and DQB1 loci, as tested by high resolution PBSC or bone marrow collected Umbilical cord blood (2 units) must be ≥ 4/6 HLA-A, B antigen, and DRB1 allele matched with recipient PATIENT CHARACTERISTICS: Platelet count > 50,000/mm^3 ANC > 1,000/mm^3 Cardiac ejection fraction > 50% (for patients ≥ 18 years of age) Fractional shortening > 50% by echocardiogram* (for patients < 18 years of age) Adjusted diffusing capacity > 50% on pulmonary function testing* Serum creatinine < 1.5 mg/dL Creatinine clearance ≥ 50 mL/min Total bilirubin < 2.0 mg/dL in the absence of a history of Gilbert disease HIV I and II negative Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception Karnofsky performance status (PS) ≥ 70% or Lansky PS ≥ 70% (for patients proceed to AHSCT) No active and uncontrolled infection at time of transplantation including active infection with Aspergillus or other mold (for patients proceed to AHSCT) NOTE: *measured since last chemotherapy PRIOR CONCURRENT THERAPY: See Disease Characteristics No prior allogeneic transplantation No more than 1 prior autologous transplantation No inability to complete planned cytoreduction due to therapy complications
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Miguel-Angel Perales, MD
Organizational Affiliation
Memorial Sloan Kettering Cancer Center
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Juliet Barker, MBBS
Organizational Affiliation
Memorial Sloan Kettering Cancer Center
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Tanya Trippett, MD
Organizational Affiliation
Memorial Sloan Kettering Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Memorial Sloan-Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States

12. IPD Sharing Statement

Links:
URL
https://www.mskcc.org/
Description
Memorial Sloan Kettering Cancer Center

Learn more about this trial

Combination Chemotherapy Followed by Donor Stem Cell Transplant in Treating Patients With Relapsed or High-Risk Primary Refractory Hodgkin Lymphoma

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